Animal models of human disease are important comparative tools in research. The development and characterization of an HIV-1 animal model such as the chimpanzee, for persistent viral infection serves just such a purpose. Chimpanzees (pantroglodytes) are uniquely susceptible to intravenous infection; as little as 0.2 pl or 0.5 syncytial-forming units of tissue culture-derived virus is capable of causing an infection. Viruses can be readily reisolated from their peripheral blood mononuclear cells (C-PBMCs) for long periods (months to years).Seroconversion occurs within two weeks of initial virus isolation and antibodies made, recognize all major viral proteins. No cell-free virus can be detected in the plasma and no immunologic or cytologic abnormality has been characterized for over four years. Virus appears to be contained in the circulating peripheral lymphocyte pool only. Comparative in vitro infections of human and C-PBMCS leads to reduced virus replication and minimal virus-associated cytopathology as compared to HIV-1-infected human PBMCS. Comparative studies in an accidentally infected lab worker, who received a similar virus strain as our chimpanzee studies, suggest similar serologic and virologic post-infectious events. The infected human responds as the chimpanzee does with a type-specific neutralizing antibody followed by a more broadly reactive response. The human, however, has an overall slower and lower titered response. Also, neutralization-resistant variants are reisolated over a 28-month period and show point mutations in the immunodominant neutralization epitope.